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Regulation of Cell Division AP Biology 2008-2009 Overview of Cell Cycle Control Two irreversible points in cell cycle replication of genetic material separation of sister chromatids Checkpoints process is assessed & possibly halted sister chromatids centromere single-stranded AP Biology chromosomes double-stranded chromosomes Checkpoint control system Checkpoints cell cycle controlled by STOP & GO chemical signals at critical points signals indicate if key cellular processes have been completed correctly AP Biology Checkpoint control system M Mitosis 3 major checkpoints: G1/S can DNA synthesis begin? G2/M has DNA synthesis been completed correctly? commitment to mitosis spindle checkpoint are all chromosomes attached to spindle? can sister chromatids separate correctly? AP Biology G2 Gap 2 S Synthesis G1 Gap 1 G0 Resting Activation of cell division How do cells know when to divide? cell communication signals chemical signals in cytoplasm give cue signals usually mean proteins activators inhibitors AP Biology experimental evidence: Can you explain this? Cell cycle signals Cell cycle controls cyclins regulatory proteins levels cycle in the cell Cdks cyclin-dependent kinases phosphorylates cellular proteins activates or inactivates proteins Cdk-cyclin complex triggers passage through different stages of cell cycle AP Biology Spindle checkpoint G2 / M checkpoint Chromosomes attached at metaphase plate • Replication completed • DNA integrity Active Inactive Inactive Cdk / G2 cyclin (MPF) M Active APC C cytokinesis mitosis G2 G1 S MPF = Mitosis Promoting Factor APC = Anaphase AP BiologyComplex Promoting Cdk / G1 cyclin Active G1 / S checkpoint Inactive • Growth factors • Nutritional state of cell • Size of cell External signals Growth factors coordination between cells protein signals released by body cells that stimulate other cells to divide density-dependent inhibition crowded cells stop dividing AP Biology Growth factor signals growth factor nuclear pore nuclear membrane P P cell division cell surface receptor protein kinase cascade Cdk P P E2F chromosome P APcytoplasm Biology nucleus Example of a Growth Factor Platelet Derived Growth Factor (PDGF) made by platelets in blood clots binding of PDGF to cell receptors stimulates cell division in connective tissue heal wounds AP Biology Growth Factors and Cancer Growth factors can create cancers proto-oncogenes normally activates cell division growth factor genes become oncogenes (cancer-causing) when mutated if switched “ON” can cause cancer example: RAS (activates cyclins) tumor-suppressor genes normally inhibits cell division if switched “OFF” can cause cancer example: p53 AP Biology Cancer & Cell Growth Cancer is essentially a failure of cell division control unrestrained, uncontrolled cell growth What control is lost? lose checkpoint stops gene p53 plays a key role in G1/S restriction point p53 protein halts cell division if it detects damaged DNA p53 is the options: Cell Cycle Enforcer stimulates repair enzymes to fix DNA forces cell into G0 resting stage keeps cell in G1 arrest causes apoptosis of damaged cell ALL cancers have to shut down p53 activity AP Biology Development of Cancer Cancer develops only after a cell experiences ~6 key mutations (“hits”) unlimited growth turn on growth promoter genes ignore checkpoints turn off tumor suppressor genes (p53) escape apoptosis turn off suicide genes immortality = unlimited divisions turn on chromosome maintenance genes It’s like an out-of-control car with many systems failing! promotes blood vessel growth turn on blood vessel growth genes AP Biology overcome anchor & density dependence turn off touch-sensor gene What causes these “hits”? Mutations in cells can be triggered by AP Biology UV radiation chemical exposure radiation exposure heat cigarette smoke pollution age genetics Tumors Mass of abnormal cells Benign tumor abnormal cells remain at original site as a lump p53 has halted cell divisions most do not cause serious problems & can be removed by surgery Malignant tumor cells leave original site lose attachment to nearby cells carried by blood & lymph system to other tissues start more tumors = metastasis impair functions of organs throughout body AP Biology Traditional treatments for cancers Treatments target rapidly dividing cells high-energy radiation kills rapidly dividing cells chemotherapy stop DNA replication stop mitosis & cytokinesis stop blood vessel growth AP Biology
